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非重组群体中选择性清除过程中的中性遗传多样性。

Neutral genetic diversity during selective sweeps in non-recombining populations.

作者信息

Kaushik Sachin, Jain Kavita, Johri Parul

机构信息

Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Integrative Program for Biological & Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

出版信息

Genetics. 2025 Aug 4. doi: 10.1093/genetics/iyaf142.

Abstract

Selective sweeps, resulting from the spread of beneficial, neutral, or deleterious mutations through a population, shape patterns of genetic variation at linked neutral sites. While many theoretical, computational, and statistical advances have been made in understanding the genomic signatures of selective sweeps in recombining populations, relatively less is understood in populations with little/no recombination, and arbitrary dominance and inbreeding. Using diffusion theory, we obtain the full expression for the expected site frequency spectrum (SFS) at linked neutral sites immediately post and during the fixation of moderately or strongly beneficial mutations. When a single hard sweep occurs, the SFS decays as 1/x for low derived allele frequencies (x), similar to the neutral SFS at equilibrium, whereas at higher derived allele frequencies, it follows a 1/x2 power law as also seen in a rapidly expanding neutral population. We show that these power laws are universal in the sense that they are independent of the dominance and inbreeding coefficients, and also characterize the SFS during the sweep. Additionally, we find that the derived allele frequency where the SFS shifts from the 1/x to 1/x2 power law is inversely proportional to the selection strength; thus under strong selection, the SFS follows the 1/x2 dependence for most allele frequencies. When clonal interference is pervasive, the SFS immediately post-fixation becomes U-shaped and can be approximated by the equilibrium SFS of selected sites. Our results will be important in developing statistical methods to infer the timing and strength of recent selective sweeps in asexual populations, genomic regions that lack recombination, and clonally propagating tumor populations.

摘要

选择性清除是指有益、中性或有害突变在种群中扩散,从而塑造了连锁中性位点的遗传变异模式。虽然在理解重组种群中选择性清除的基因组特征方面已经取得了许多理论、计算和统计上的进展,但对于几乎没有/没有重组、具有任意显性和近亲繁殖的种群,人们了解得相对较少。利用扩散理论,我们得到了在中等或强有益突变固定后及固定期间连锁中性位点预期位点频率谱(SFS)的完整表达式。当发生单次硬清除时,对于低衍生等位基因频率(x),SFS以1/x的形式衰减,类似于平衡时的中性SFS,而在较高衍生等位基因频率下,它遵循1/x²幂律,这在快速扩张的中性种群中也可以看到。我们表明,这些幂律具有普遍性,因为它们与显性和近亲繁殖系数无关,并且也表征了清除过程中的SFS。此外,我们发现SFS从1/x幂律转变为1/x²幂律的衍生等位基因频率与选择强度成反比;因此,在强选择下,对于大多数等位基因频率,SFS遵循1/x²依赖性。当克隆干扰普遍存在时,固定后立即的SFS会变成U形,并且可以用选择位点的平衡SFS来近似。我们的结果对于开发统计方法以推断无性种群、缺乏重组的基因组区域和克隆繁殖的肿瘤种群中近期选择性清除的时间和强度将具有重要意义。

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